1AGN

X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE

1AGN の概要

• エントリーDOI: 10.2210/pdb1agn/pdb
• 分子名称: HUMAN SIGMA ALCOHOL DEHYDROGENASE, ZINC ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P40394
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 163988.09

構造登録者

Hurley, T.D.,Xie, P. (登録日: 1996-06-04, 公開日: 1997-03-12, 最終更新日: 2024-02-07)

主引用文献

Xie, P.,Parsons, S.H.,Speckhard, D.C.,Bosron, W.F.,Hurley, T.D.
X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity.
J.Biol.Chem., 272:18558-18563, 1997

PubMed Abstract: The structural determinants of substrate recognition in the human class IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined through x-ray crystallography and site-directed mutagenesis. The crystal structure of sigmasigma ADH complexed with NAD+ and acetate was solved to 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share 69% sequence identity and exhibit dramatically different kinetic properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma substrate-binding pocket, relative to the beta1beta1 isoenzyme. The nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1 isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist widens the substrate pocket in the vicinity of the catalytic zinc and may contribute to this isoenzyme's high Km for small substrates. The presence of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma substrate pocket and may explain the substantially decreased Km values with increased chain length of substrates in sigmasigma ADH. The kinetic properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that widening the middle region of the substrate pocket increases Km by weakening the interactions between the enzyme and smaller substrates while not affecting the binding of longer alcohols, such as hexanol and retinol.

PubMed: 9228021
DOI: 10.1074/jbc.272.30.18558

実験手法

X-RAY DIFFRACTION (3 Å)